The advent of next-generation sequencing has introduced new opportunities in analyzing gene expression data. Research in systems biology has taken advantage of these opportunities by gleaning insights into gene regulatory networks through the analysis of gene association networks. Contrasting networks from different populations can reveal the many different roles genes fill, which can lead to new discoveries in gene function. Pathologies can also arise from aberrations in these gene-gene interactions. Exposing these network irregularities provides a new avenue for understanding and treating diseases. A general framework for integrating known gene regulatory pathways into a differential network analysis between two populations is proposed. The framework importantly allows for any gene-gene association measure to be used, and inference is carried out through permutation testing. A simulation study investigates the performance in identifying differentially connected genes when incorporating known pathways, even if the pathway knowledge is partially inaccurate. Another simulation study compares the general framework with four state-of-the-art methods. Two RNA-seq datasets are analyzed to illustrate the use of this framework in practice. In both examples, the analysis reveals genes and pathways that are known to be biologically significant along with potentially novel findings that may be used to motivate future research.
机构:
Samsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
Samsung Genome Inst, Seoul, South KoreaSamsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
Lee, Eunjin
;
Huh, Nam
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机构:
Samsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South KoreaSamsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
Huh, Nam
;
Park, Taesung
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机构:
Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea
Seoul Natl Univ, Dept Stat, Seoul, South KoreaSamsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
机构:Childrens Hosp Los Angeles, USC Keck Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA
Ara, Tasnim
;
DeClerck, Yves A.
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Childrens Hosp Los Angeles, USC Keck Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, USC Keck Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA
机构:
Samsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
Samsung Genome Inst, Seoul, South KoreaSamsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
Lee, Eunjin
;
Huh, Nam
论文数: 0引用数: 0
h-index: 0
机构:
Samsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South KoreaSamsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
Huh, Nam
;
Park, Taesung
论文数: 0引用数: 0
h-index: 0
机构:
Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea
Seoul Natl Univ, Dept Stat, Seoul, South KoreaSamsung Adv Inst Technol, Suwon 443803, Gyeonggi Do, South Korea
机构:Childrens Hosp Los Angeles, USC Keck Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA
Ara, Tasnim
;
DeClerck, Yves A.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Los Angeles, USC Keck Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, USC Keck Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA